British Journal of Ophthalmology, 1979, 63, 699-703
Orbitofacial mucormycosis with unusual pathological features* ALBERT,
LESSER,2
CYKIERT,2
Z. NICHOLAS ZAKOV' From the 'Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, and 2Yale University School of Medicine, New Haven, Connecticut, USA
A 52-year-old man with mild diabetes and acute stem cell leukaemia developed an orbitofacial mucormycosis. Cultures showed the fungus to be Rhizopus oryzae. Vigorous treatment with amphotericin B and with other bactericidal and bacteriostatic antibiotics for a concurrent sepsis failed to suppress the infections, and the patient died. On post-mortem examination characteristic haematoxylin-staining, broad, aseptate fungal hyphae were found in the right eye, orbit, and lung. A striking and unusual feature of this case is the presence of brightly biiefringent crystals within the severely degenerated eye. These were found by histochemical staining and x-ray diffraction studies to be calcium salts of fatty acids, apparently liberated from necrotic adipose tissue of the orbit. SUMMARY
looking lesion in his right superior gingiva. One month prior to this admission he had been admitted to another hospital for evaluation of severe low back pain, the onset of which followed lifting a heavy load. Medical and neurological examinations at that time were within normal limits. Laboratory studies including complete and differential blood count, serum electrolytes, liver function tests, and acid phosphatase were within normal limits. A diagnosis of diabetes mellitus was made on the basis of raised fasting serum glucose and abnormal glucose tolerance test. Radiological examinations at the time of the first admission were within normal limits, with the exception of a possible ruptured lumbar disc. The diabetes was controlled by diet 1960; Ferry, 1960; Gass, 1961a; Gass, 1961b; alone, and the patient was discharged on analgesics Straatsma et al., 1962; Frangois and Rysselaere, 1 week after admission. At the time of the second admission the patient 1972; Schwartz, 1977). complained of persistent low back pain, loss of appetite, weight loss, and general malaise. Positive Case report findings on physical examination included a palpable A 52-year-old white male with acute stem cell spleen, mild abdominal distension, and highly leukaemia developed a small, dark, gangrenous- tympanic bowel sounds. A complete blood count revealed haemoglobin of 11 -2 g/dl, a white blood count of 22 x 109/1 composed almost entirely of * Read before the Eastern Ophthalmic Pathology Society Meeting, McGill University, Montreal, Quebec, September blast cells of stem cell or myeloblastic origin, and a 1976 (Dr Albert) platelet count of 98 x 109/l. A diagnosis of acute stem cell leukaemia was made. Other laboratory Correspondence to Dr Daniel M. Albert, Howe Laboratory, studies and radiological examinations were within Massachusetts Eye and Ear Infirmary, 243 Charles Street, normal limits. Boston, MA 02114, USA 699
Mucormycosis, or phycomycosis, is an infection caused by one of a variety of fungi belonging to the class Phycomycetes. Although these fungi are usually saprophytic and ubiquitous in nature, they can cause serious and rapidly fatal infections in man. Usually the patients who manifest this infection have a predisposing debilitating condition, among the most common of which are diabetes with acidosis, diarrhoea and dehydration, renal failure, cirrhosis, leukaemia or other lymphoproliferative disorders, and severe burns. In addition steroids, antibiotics, and cytotoxic agents have been strongly implicated both clinically and experimentally as predisposing agents for this infection. Excellent reviews of this subject are available (Hutter, 1959; McBride et al.,
700
Daniel M. Albert, Robert L. Lesser, Robert C. Cykiert, and Z. Nicholas Zakov
Fig. 1 Appearance of the patient with right orbitofacial mucormycosis
normal limits. The iris, lens, and anterior vitreous body appeared normal on the right. The view of the right fundus was hazy, but no discrete vitreous or retinal lesions were seen. The overall impression was that of a right eye with no light perception owing to a phycomycosis of the right face and orbit. A right cavernous sinus thrombosis was highly suspected. Results of examination of the left eye were within normal limits. Although treatment with amphotericin B seemed to prevent further extension of the facial lesion, the patient soon developed a partial atelectasis of the right lung, intestinal obstruction, and became septic, with Escherichia coli and a Bacteroides species being cultured from the blood. Treatment with gentamicin and cephalothin in addition to the amphotericin B did not lead to improvement of the patient's condition. The patient died in septic shock 6 weeks after admission to the hospital and approximately 3 weeks after developing the orbitofacial phycomycosis. PATHOLOGY
The patient was kept in isolation and was followed up with frequent peripheral and bone marrow smears. Treatment with a combination of thioguanine and cytosine arabinoside eventually led to anaplastic marrow and necessitated platelet and white blood cell transfusions. Three weeks after the second admission the gingival lesion developed; within days it had spread to the cheek and soon involved the entire right side of the face (Fig. 1). Numerous attempts at bacterial culture from this widespread lesion were negative. Biopsy of the lesion showed numerous fungi with broad septate hyphae embedded in a matrix of chronic inflammatory cells and necrotic tissue. A culture of the fungus from the facial lesion was identified as Rhizopus oryzae. Treatment with intravenous amphotericin B was begun. An ophthalmological examination was done about 2 weeks after the development of facial mucormycosis. It showed that vision in the right eye was of no light perception and in the left eye was 6/12 (20/40) with best correction. The right periorbital area was necrotic and indurated. The right eye was proptosed 6 mm, and no extraocular movements could be elicited. Manipulation of the right lids was done with difficulty because of pain and caused some bleeding. The cornea was ulcerated; the conjunctiva of the right eye showed severe injection. The right eye was softer to palpation than the left. On slit-lamp biomicroscopy of the right eye corneal ulceration was evident; the anterior chamber was deep, and no hypopyon was seen. Findings on slit-lamp biomicroscopy of the left eye were within
Necropsy revealed a septicaemia, stem cell leukaemia, small bowel perforation with peritonitis and abscess formation, gastric mucosal petechiae, haemorrhagic pyelitis, splenic abscesses, and widespread mucormycosis, with fungi present in the entire right face, orbit, and eye as well as the lung. Eye pathology (AFIP Accession No. 1546176). The right eye was found to be a necrotic grey-black mass measuring 21 x 27 mm. It had no identifiable external landmarks and did not transilluminate light. The cornea and pupil could not be identified. The optic nerve was 14 mm long and appeared normal. The globe was opened anteroposteriorly. The ciliary body and lens were not distinguishable. The vitreous was replaced by viscid, mottled material. The retina, choroid, and optic disc could not be identified on gross examination. The sclera was largely absent, but where present, was thickened. Microscopically the right eye was found to be extremely disorganised, with marked degeneration of all layers (Fig. 2). Only small sections of sclera and optic nerve were intact. The remainder of the globe resembled fibrous and fatty tissues with a diffuse infiltration of strongly hematoxylin-staining long, broad, non-septate hyphae, consistent with a fungus belonging to the class Phycomycetes (Fig. 3). Within the globe were many crystals which stained intensely with alizarin red (Fig. 4), and were brightly birefringent when observed under polarised light. These crystals did not stain with haematoxylin and eosin, periodic acid-Schiff (PAS), Gromori methenamine silver (GMS), or von Kossa stain. Johnson's 'bubble test' for calcium oxalate was negative
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Orbitofacial mucormycosis with unusual pathological features* ALBERT,
LESSER,2
CYKIERT,2
Z. NICHOLAS ZAKOV' From the 'Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, and 2Yale University School of Medicine, New Haven, Connecticut, USA
A 52-year-old man with mild diabetes and acute stem cell leukaemia developed an orbitofacial mucormycosis. Cultures showed the fungus to be Rhizopus oryzae. Vigorous treatment with amphotericin B and with other bactericidal and bacteriostatic antibiotics for a concurrent sepsis failed to suppress the infections, and the patient died. On post-mortem examination characteristic haematoxylin-staining, broad, aseptate fungal hyphae were found in the right eye, orbit, and lung. A striking and unusual feature of this case is the presence of brightly biiefringent crystals within the severely degenerated eye. These were found by histochemical staining and x-ray diffraction studies to be calcium salts of fatty acids, apparently liberated from necrotic adipose tissue of the orbit. SUMMARY
looking lesion in his right superior gingiva. One month prior to this admission he had been admitted to another hospital for evaluation of severe low back pain, the onset of which followed lifting a heavy load. Medical and neurological examinations at that time were within normal limits. Laboratory studies including complete and differential blood count, serum electrolytes, liver function tests, and acid phosphatase were within normal limits. A diagnosis of diabetes mellitus was made on the basis of raised fasting serum glucose and abnormal glucose tolerance test. Radiological examinations at the time of the first admission were within normal limits, with the exception of a possible ruptured lumbar disc. The diabetes was controlled by diet 1960; Ferry, 1960; Gass, 1961a; Gass, 1961b; alone, and the patient was discharged on analgesics Straatsma et al., 1962; Frangois and Rysselaere, 1 week after admission. At the time of the second admission the patient 1972; Schwartz, 1977). complained of persistent low back pain, loss of appetite, weight loss, and general malaise. Positive Case report findings on physical examination included a palpable A 52-year-old white male with acute stem cell spleen, mild abdominal distension, and highly leukaemia developed a small, dark, gangrenous- tympanic bowel sounds. A complete blood count revealed haemoglobin of 11 -2 g/dl, a white blood count of 22 x 109/1 composed almost entirely of * Read before the Eastern Ophthalmic Pathology Society Meeting, McGill University, Montreal, Quebec, September blast cells of stem cell or myeloblastic origin, and a 1976 (Dr Albert) platelet count of 98 x 109/l. A diagnosis of acute stem cell leukaemia was made. Other laboratory Correspondence to Dr Daniel M. Albert, Howe Laboratory, studies and radiological examinations were within Massachusetts Eye and Ear Infirmary, 243 Charles Street, normal limits. Boston, MA 02114, USA 699
Mucormycosis, or phycomycosis, is an infection caused by one of a variety of fungi belonging to the class Phycomycetes. Although these fungi are usually saprophytic and ubiquitous in nature, they can cause serious and rapidly fatal infections in man. Usually the patients who manifest this infection have a predisposing debilitating condition, among the most common of which are diabetes with acidosis, diarrhoea and dehydration, renal failure, cirrhosis, leukaemia or other lymphoproliferative disorders, and severe burns. In addition steroids, antibiotics, and cytotoxic agents have been strongly implicated both clinically and experimentally as predisposing agents for this infection. Excellent reviews of this subject are available (Hutter, 1959; McBride et al.,
700
Daniel M. Albert, Robert L. Lesser, Robert C. Cykiert, and Z. Nicholas Zakov
Fig. 1 Appearance of the patient with right orbitofacial mucormycosis
normal limits. The iris, lens, and anterior vitreous body appeared normal on the right. The view of the right fundus was hazy, but no discrete vitreous or retinal lesions were seen. The overall impression was that of a right eye with no light perception owing to a phycomycosis of the right face and orbit. A right cavernous sinus thrombosis was highly suspected. Results of examination of the left eye were within normal limits. Although treatment with amphotericin B seemed to prevent further extension of the facial lesion, the patient soon developed a partial atelectasis of the right lung, intestinal obstruction, and became septic, with Escherichia coli and a Bacteroides species being cultured from the blood. Treatment with gentamicin and cephalothin in addition to the amphotericin B did not lead to improvement of the patient's condition. The patient died in septic shock 6 weeks after admission to the hospital and approximately 3 weeks after developing the orbitofacial phycomycosis. PATHOLOGY
The patient was kept in isolation and was followed up with frequent peripheral and bone marrow smears. Treatment with a combination of thioguanine and cytosine arabinoside eventually led to anaplastic marrow and necessitated platelet and white blood cell transfusions. Three weeks after the second admission the gingival lesion developed; within days it had spread to the cheek and soon involved the entire right side of the face (Fig. 1). Numerous attempts at bacterial culture from this widespread lesion were negative. Biopsy of the lesion showed numerous fungi with broad septate hyphae embedded in a matrix of chronic inflammatory cells and necrotic tissue. A culture of the fungus from the facial lesion was identified as Rhizopus oryzae. Treatment with intravenous amphotericin B was begun. An ophthalmological examination was done about 2 weeks after the development of facial mucormycosis. It showed that vision in the right eye was of no light perception and in the left eye was 6/12 (20/40) with best correction. The right periorbital area was necrotic and indurated. The right eye was proptosed 6 mm, and no extraocular movements could be elicited. Manipulation of the right lids was done with difficulty because of pain and caused some bleeding. The cornea was ulcerated; the conjunctiva of the right eye showed severe injection. The right eye was softer to palpation than the left. On slit-lamp biomicroscopy of the right eye corneal ulceration was evident; the anterior chamber was deep, and no hypopyon was seen. Findings on slit-lamp biomicroscopy of the left eye were within
Necropsy revealed a septicaemia, stem cell leukaemia, small bowel perforation with peritonitis and abscess formation, gastric mucosal petechiae, haemorrhagic pyelitis, splenic abscesses, and widespread mucormycosis, with fungi present in the entire right face, orbit, and eye as well as the lung. Eye pathology (AFIP Accession No. 1546176). The right eye was found to be a necrotic grey-black mass measuring 21 x 27 mm. It had no identifiable external landmarks and did not transilluminate light. The cornea and pupil could not be identified. The optic nerve was 14 mm long and appeared normal. The globe was opened anteroposteriorly. The ciliary body and lens were not distinguishable. The vitreous was replaced by viscid, mottled material. The retina, choroid, and optic disc could not be identified on gross examination. The sclera was largely absent, but where present, was thickened. Microscopically the right eye was found to be extremely disorganised, with marked degeneration of all layers (Fig. 2). Only small sections of sclera and optic nerve were intact. The remainder of the globe resembled fibrous and fatty tissues with a diffuse infiltration of strongly hematoxylin-staining long, broad, non-septate hyphae, consistent with a fungus belonging to the class Phycomycetes (Fig. 3). Within the globe were many crystals which stained intensely with alizarin red (Fig. 4), and were brightly birefringent when observed under polarised light. These crystals did not stain with haematoxylin and eosin, periodic acid-Schiff (PAS), Gromori methenamine silver (GMS), or von Kossa stain. Johnson's 'bubble test' for calcium oxalate was negative
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